P.1013 Combining Monoclonal Antibodies with 1,25(OH)2D3 Treatment to Prolong the Survival Time of Cardiac Allograft in Accelerated Rejection Models of Mice
Saturday August 20, 2016 from 17:00 to 18:30
Hall 5FG-Level 5
Presenter

Yaguang Li, People's Republic of China

Organ Transplantation Institute of Xiamen University

Abstract

Combining monoclonal antibodies with 1,25(OH)2D3 treatment to prolong the survival time of cardiac allograft in accelerated rejection models of mice

Yan Guoliang1,2, Xu Shuangyue1,2, Li Yaguang1,2, Qi Zhongquan1,2.

1Organ Transplantation Institute, Xiamen University, Xiamen, People's Republic of China; 2Fujian Provincial Key Laboratory, Organ and Tissue Regeneration, Xiamen, People's Republic of China

In this study, we investigated the combination of 1,25(OH)2D3 and monoclonal antibodies anti-CD154/anti-LFA-1 to induce long-lived heart allograft acceptance in memory T cells-based adoptive mice model. The protective effects on grafts by different treatments were evaluated and the effective combination treatment and its action mechanism was explored.

In the transplantation model of adoptive transferred alloreactive T cells, the grafts would have the longest survival time by combining costimulation blockade which could be 80 days maximum. It was declared in pathology that the lymphocytic infiltration and the damage of tissue structure was lightest. The levels of IL-2, IFN-γ and IL-10 were obviously down-regulated in Group 1,25(OH)2D3 and Ab+1,25(OH)2D3, while the gene expression levels of TGF-β and Foxp3 were up-regulated. It’s suggested that both of the treatments could increase the expression of Tregs in grafts. Detected by Flow Cytometry Method, we found that the alloreactivity and the proportion of memory CD4+ and CD8+ T cells were obviously decreased with treatment of Group 1,25(OH)2D3 and Ab+1,25(OH)2D3. The grafts could survival for a long time off the drugs, which was related with inducing numerous Tregs.

The combined recipe treatment could induce Th1 transdifferentiated to Th2. This treatment not only could significantly decrease the immune reaction of grafts and receptors, but also induce numerous Th3 phenotype which secreted TGF-β, and increased the proportion of Tregs.


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